5-aminohexahydropyrimidines and process for preparing same



Patented Oct. 16, 1945 -AMINOHEXAHYDROPYRI1HIDINES AND PROCESS FORPREPARING SAME Murray Senkus, Terre Haute, Ind, assignor to CommercialSolvents Corporation, Terre Haute,

Ind., a corporation of Maryland No Drawing. Application July 29, 1944,Serial No. 547,282

6 Claims.

My invention relates to a new series of nitrogen-containing compounds.More particularly it relates to 5-aminohexahydropyrimidines and to aprocess for their preparation. Such compounds may be represented by thefollowing structural formula:

wherein R may be either hydrogen, aryl, alkyl, or hydroxymethyl and Rmay be alkyl, aralkyl, aryl, 2-hydroxyalkyl, dialkylaminoalkyl, or 3,5-dioxacyclohexyl.

The 5-aminohexahydropyrimidines of my invention can be prepared bycatalytic hydrogenation of the corresponding B-nitrohexahydropyrimidinesin the liquid phase under pressure. Specifically this process iseffected by subjecting the aforesaid nitro derivatives to hydrogenationat normal or elevated temperatures in the pres ence of a suitablehydrogenation catalyst and a solvent at a temperature which may varyfrom about 25 to not substantially in excess of 100 C. In general, anyhydrogenation catalyst which is active within the aforesaid temperaturerange may be employed. For the majority of purposes, however, I havefound it preferable to utilize Raney nickel. The hydrogenation reactionin general may be effected at hydrogen pressures ranging from about 500pounds to pressures slightly below those which tend to cleave thehexahydropyrimidine ring. I have found it preferable however to carryout such reactions at a pressure of approximately 1,000 pounds persquare inch and at temperatures of between about 25 and 70 C. Suitablesolvents which may be utilized in the reduction step are the loweraliphatic alcohols such as methanol, ethanol, and the like.

After the reaction is complete as may be evidenced by the failure ofadditional hydrogen absorption, the catalyst is separated from thereaction mixture by filtration and the solvent is distilled off. The5-amino-hexahydropyrimidines obtained in this manner are in generalliquids and may be further purified by fractional distillation underhigh vacuum.

The 5-nitrohexahydropyrimidines employed as starting materials for thepreparation of the compounds of my invention are prepared by reacting asuitable primary amine with a nitrohydrocarbon having the nitro groupattached to a primary carbon atom in the presence of formaldehyde, thelatter being present in a molar ratio of about three to one of thenitrohydrocarbon and two moles of the primary amine. These5-nitrohexahydropyrimidines may be either liquids or solids and can bepurified in accordance with conventional methods, A more detaileddescription of the methods by which such compounds can be prepared willbe found in my copending application, U. S. Serial No. 547,281, filedJuly 29, 1944.

My invention may be further illustrated by the following specificexample.

EXAMPLE A mixture consisting of 24.0 g. of 5-nitro-5-methyl-1,3-dibenzylhexahydropyrimidine, 400 ml.

of methanol and 10 g. of Raney nickel catalyst of about 25 C. As thereduction proceeded,

however, the temperature was gradually increased to approximately C. Thehydrogenation required a period of about two hours, during which timethe reaction mixture was constantly agitated. After absorption ofhydrogen had ceased, the reaction mixture was withdrawn from thehydrogenation apparatus, the catalyst removed from the solution byfiltration and the methanol separated from the reaction mixture by meansof fractional distillation. The residue thus obtained was then subjectedto fractional distillation under high vacuum and 201 g. of 5-amino-5-methyl-1,3-dibenzylhexahydropyrimidine boiling at 178 C. (0.6 mm.) wascollected.

The 5-aminohexahydropyrimidines of the present invention are eithercolorless liquids or white crystalline solids, the lower molecularweight members of the series being soluble in water, methanol, acetone,petroleum ether and benzene, while the higher molecular weight compounds2. 5-amino-5-methy1-1,3 dibenzylhexahydropyrimidine.

3. 5-amino-5 methyl 1,3 diisopropylhexahydropyrimidine.

4. 5-amino 5 hydroxymethyl-1,3-diisopropyl-hexahydropyrimidine.

5. A process for the preparation of fi-aminohexahydropyrimidines, whichcomprises sub- Table Per cent nitro S-aminohexahydropyrimidine ggi gggg(158 no Calcd. Found 5-amino-1,3-dibcnzyl-fi-methylhexahydropyrimdin 178(0. 6) 1.0484 l. 5659 14. 23 14. 155-amino-1,3,5-trimethylhexahydropyrimidine.. 69. (10) '0. 9039 1. 470429. 37 29. 37 fi-amino-1,3-dimethy1-5phenylhcxahydropyfimidme 115-117(0. 1) 1. 0053 1. 5368 20. 49 19.-amino-1,3-diisopropylhexahydropyrimidine 1057106 0; 8794 1. 4569. 22.22. 71 fi-amino-l,3-diisopropyl-5-hydroxymethylhexahydropyn "111 014) 71; 0136 1. 4845 19. 53 19. 225-amino-1,3-diisopropy1-5-methy1hexahydrdpyrimidine (10) 0; 8828 1. 4577 21. 10 21. 025-amin0-1,3bis(l-methylheptyl)-5-methy1hexahydropyrim1dih 16:71 (0. 5)0.8548 1. 4622 12. 39 12.44 5-amino-1,3-bis(3-dimethy1au1ino-2,2-dimethylpropyl)-5-met ylhexahydropyrimidine 1.40.141 (O. 3) ;0. 9261 1. 4767 20. 53 19. 725-amino-1,3-bis(3-dibuty1aminopropyl)-5-methy1hexahydrqpxr1 A idinn2150-2331(1). 75) '0. 8892 1. 4724 15. 45 15.40 5-ami11o-1 ,3-bis (l1-dimethy1- -hydroxyethy1) -5-methy1hexahydropyrimidine. 1.: :5; J. 162,(0. 45) 1, 0544 1. 4923 16. 21 16. 01 fi-amino-LS-bisacyclohexyl)-5-methylhexahyd ropyrimidine. -177. (0. 3) 1.1028 1. 4891,13. 35 13. 2Q fi-amino-l ,3-bis 1 pyrimidine. 170-173 (0,. 25) 1.0998 1. 49,05 12. 76 j 12 94 S amino 1 3 -dipheny1- 5- 1nethy111 are (0.15) 1. 0982 1. 6143, 15. 7 2 15. 6Q

The h -aminoheiiahydropvrimidinesoi myinven- 3 jecting a5-nitrohexahydrop$ rimidine t0 hy l'Qrtion have beenf found tofbeuseful; in thefpre'paration of numerous organic compouiids." Other usesofthese products willfbeapparentfto those skilled in'theart.

My invention'now.having'been described, what d i n.

1. As new. compositions of matter, 5 amin o ste t re t e e -f genationin the liquid phase in the presence of. a hydrogenation catalyst atelevated pressure and at a temperature of from about 25 to about 100 C.

6. As new compositions of matter, fi-amino-1,3-disubstitutedhexahydropyrimidines.

MURRAY SENKUS.

